Blue cells of death mark the end of a worm’s life

Death begins with an organized and consistent pattern of change.

Never has “feeling blue” carried such a sense of finality. A new study has revealed that the simple worm (Caenorhabditis elegans) meets its death in a flash of azure. According to researchers, the blue light shows that dying may be a coordinated process that could probably be delayed.

Scientists have known for many years that cells can die in two ways. Necrosis occurs when either the cell’s machinery breaks down with age or exposure to trauma damages the cell beyond repair. Apoptosis is a programmed process triggered on demand, by which even healthy cells can undergo a series of changes resulting in an orderly death.

But when it comes to multicellular organisms (such as humans) dying, defining the exact mechanisms becomes more complicated. It cannot simply be explained by a bunch of cells dying independently. How do you define the precise moment when an animal stops being alive, and what is the sequence of events leading to death?

To answer that question, David Gems of University College London led a study published in the journal PLOS Biologythatlooked at a simple worm (Caenorhabditis elegans) dying under his microscope. This model organism is easy to study because it is tiny and completely transparent; it has a relatively short life and its genes have been studied inside-out.

What Gems and his colleagues found was that under ultraviolet light, the intestine of C. elegans would emit a blue fluorescent light as the worm was about to die. The light, termed “death fluorescence” by the researchers, got more and more intense as the worm’s cells became necrotic. The light reached its maximum intensity at the exact moment the worm died and then quickly faded away.

The finding is remarkable because the blue light was observed both for worms dying from natural causes and for stress-related death, such as being under extreme heat or cold. Starting from one end of the worm, the blue light wave would propagate along its intestine until it was dead. This ordered propagation suggested that, among multicellular organisms, death may happen through a series of coordinated “self-destruct” signals.

Gems found that the blue light was caused by the activation of a biological pathway related to calcium signalling, ultimately triggering the fluorescence of small molecules called anthranilic acids (AAs). They found that the spark of blue light was not due to the sudden production of AAs, but because of their release from acidic cellular compartments when the membranes keeping them trapped broke open upon necrosis.

When the team blocked the calcium signalling pathway, the burst could be delayed if a stress was the cause of death. However, no delay could be obtained if it was a case of age-related death. This suggests that age-related death involves more than just calcium signalling.

The work casts doubt on the idea that age-related death is simply a consequence of accumulated damage at the cellular level. It may well be that a coordinated action decides when the threshold is met. But the fact that death can now be caught in action under a microscope will help us develop and understand methods to delay it. In which case, seeing the light might be a good thing in the end.

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Starting from one end of the worm, the blue light wave would propagate along its intestine until it was dead. This ordered propagation suggested that, among multicellular organisms, death may happen through a series of coordinated “self-destruct” signals.

Haven't read the paper, but couldn't it simply be the propagation of anoxia through the organism, after circulation stops?

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Starting from one end of the worm, the blue light wave would propagate along its intestine until it was dead. This ordered propagation suggested that, among multicellular organisms, death may happen through a series of coordinated “self-destruct” signals.

Haven't read the paper, but couldn't it simply be the propagation of anoxia through the organism, after circulation stops?

Unlikely, since C. elegans has no circulatory system. The anoxia would not be observed in an orderly fashion from one end of the worm to the other, but rather in a gradual systemwide event.

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Hopefully not. That would be a disaster for the human race.

People are not mentally as flexible as they like to suppose and many times throughout history, progress in some field of knowledge has only occurred as the older generation dies off and the younger takes its place.

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

I don't know...a gene that automatically culls the population in response to viral infections has a lot going in its favor as far as protecting additional copies of itself in other organisms. If any false positives that result in termination of the organism occur when the organism is well past the peak of its reproductive activity, then they're not a major drawback.

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

It's hard to imagine a mechanism for death that can be bred through genetic selection but I can see one such path. Imagine you have organisms that have lived beyond when they should have died either through trauma or through old age. If they reproduce at this stage the offspring may not be viable, they may not be as genetically fit, etc. All they've accomplished is to consume resources that offspring of related, more viable offspring may have used.

Studies of bee hives, ants, etc. have demonstrated that it may be genetically advantageous to help closely related survive at the cost of one's own life or reproduction. (see also insects that eat their mates after copulation but those are direct progeny).

A flash of light just before death? I hope the worm's remains weren't turned to marble.

Quote:

CAMILLA: You, sir, should unmask.STRANGER: Indeed?CASSILDA: Indeed it's time. We all have laid aside disguise but you.STRANGER: I wear no mask.CAMILLA: (Terrified, aside to Cassilda.) No mask? No mask!

'If they reproduce at this stage the offspring may not be viable, they may not be as genetically fit, etc. All they've accomplished is to consume resources that offspring of related, more viable offspring may have used.'

I did consider poor offspring but thought it wouldnt be a problem as long as the worm had produced at least some good ones. The idea that it would consume all the resources with wasteful offspring is sound though.

I have now read the paper and it has a very similar hypothesis to your own, it suggests that when nutrients are scarce a mother will kill itself and its babies will consume it allowing a more efficient passing on of nutrients with the hope they will survive to find more.

The only other suggestion they had was much the same as what I was left with, they are mechanisms that are helpful for survival but have an unfortunate catastrophic failure point. (The death mechanism is quite neat producing what they call a 'necrotic wave'.)

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

It's hard to imagine a mechanism for death that can be bred through genetic selection but I can see one such path. Imagine you have organisms that have lived beyond when they should have died either through trauma or through old age. If they reproduce at this stage the offspring may not be viable, they may not be as genetically fit, etc. All they've accomplished is to consume resources that offspring of related, more viable offspring may have used.

Studies of bee hives, ants, etc. have demonstrated that it may be genetically advantageous to help closely related survive at the cost of one's own life or reproduction. (see also insects that eat their mates after copulation but those are direct progeny).

Sounds like it wasn't hard to imagine a mechanism for death at all.

Any species where death improved the survival and reproduction of an individual's offspring would therefore select for death.

Any trait that accidentally killed an individual would also be selected for so long as the individual successfully reproduced.

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Hopefully not. That would be a disaster for the human race.

People are not mentally as flexible as they like to suppose and many times throughout history, progress in some field of knowledge has only occurred as the older generation dies off and the younger takes its place.

Eh, parenthetically, that's a risk I for one am more than willing to take. Bring on the shades for the blue light of death. A spritely pace of scientific progress isn't more valuable to me than actually, you know, being alive. Nevermind the implications of the alternative position...

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Hopefully not. That would be a disaster for the human race.

People are not mentally as flexible as they like to suppose and many times throughout history, progress in some field of knowledge has only occurred as the older generation dies off and the younger takes its place.

Agreed. In the words of Lewis Black "Having an expiration date isn't a bug, it's a feature!"

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

It's hard to imagine a mechanism for death that can be bred through genetic selection but I can see one such path. Imagine you have organisms that have lived beyond when they should have died either through trauma or through old age. If they reproduce at this stage the offspring may not be viable, they may not be as genetically fit, etc. All they've accomplished is to consume resources that offspring of related, more viable offspring may have used.

Studies of bee hives, ants, etc. have demonstrated that it may be genetically advantageous to help closely related survive at the cost of one's own life or reproduction. (see also insects that eat their mates after copulation but those are direct progeny).

Sounds like it wasn't hard to imagine a mechanism for death at all.

Any species where death improved the survival and reproduction of an individual's offspring would therefore select for death.

Any trait that accidentally killed an individual would also be selected for so long as the individual successfully reproduced.

I need you guys to talk to me mum, .. Cause seriously, Its time for her to go.

I would be very curious to know how human knowledge would progress in a timeline where this "death flash" was not in the visible spectrum. Now that we've seen this flash in one species we can start looking in other species, but what if the worm's death flash was in UV? This seems like one of those discoveries that might drastically change the course of death research, and we might never have found it if the light had been shifted by a few wavelengths.

I would be very curious to know how human knowledge would progress in a timeline where this "death flash" was not in the visible spectrum. Now that we've seen this flash in one species we can start looking in other species, but what if the worm's death flash was in UV? This seems like one of those discoveries that might drastically change the course of death research, and we might never have found it if the light had been shifted by a few wavelengths.

Mind you, it was a flash when exposed to UV light. It's a fluorescence reaction that only emits light because the acid in question interacted with the stimulation light.

Why did hardier more prolific worms develop anything other than using the cells for as long as possible? It seems really counter intuitive that an apparently more complex system would take its place providing a mechanism to die earlier than may be necessary. (As demonstrated when they could prolong the worms life after stress.)

The only thing I can think of is that the mechanism is somehow tied in to other systems that aid in survival and that its an unfortunate consequence of that. (No doubt there would be good uses for signalling of that nature it wouldnt be a big leap to have also included a death signal in that mechanism.)

It's hard to imagine a mechanism for death that can be bred through genetic selection but I can see one such path. Imagine you have organisms that have lived beyond when they should have died either through trauma or through old age. If they reproduce at this stage the offspring may not be viable, they may not be as genetically fit, etc. All they've accomplished is to consume resources that offspring of related, more viable offspring may have used.

Studies of bee hives, ants, etc. have demonstrated that it may be genetically advantageous to help closely related survive at the cost of one's own life or reproduction. (see also insects that eat their mates after copulation but those are direct progeny).

Sounds like it wasn't hard to imagine a mechanism for death at all.

Any species where death improved the survival and reproduction of an individual's offspring would therefore select for death.

Any trait that accidentally killed an individual would also be selected for so long as the individual successfully reproduced.

It's especially relevant in humans, where offspring viability nosedives in the mid-40's. No offense to those of you with special needs children, but in comparison to a normal child, raising a child with down's syndrome is a life-long task. In nature, it's entirely feasible that an organism would possess genes that attempted to prevent this by initiating cell death.

I suspect all that this work shows is that a signaling cascade centered on the calcium system is a central part of the event of dying. That result reinforces the central role of calcium based signaling in organizing the activity of eukaryotic cells and metazoan organisms. But, it does not say much about the variety of conditions that are able to reach the threshold where the signaling system is no longer able to maintain homeostasis and enters a relatively organized death spiral.

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

In the long run I don't think it is a question of "can this machinery be put on hold" but rather "should this machinery be put on hold".

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Hopefully not. That would be a disaster for the human race.

People are not mentally as flexible as they like to suppose and many times throughout history, progress in some field of knowledge has only occurred as the older generation dies off and the younger takes its place.

Agreed. "The old makes way for the new." Or, my other favorite: "Whatever has a beginning, Neo, also has an end."

So, it sounds like death is not just an accident of evolution. Species where individual are predisposed to a certain death may survive better. So evolution has selected for machinery to bring about the demise of individuals. The question for humans will be: can this machinery be put on hold?

Hopefully not. That would be a disaster for the human race.

People are not mentally as flexible as they like to suppose and many times throughout history, progress in some field of knowledge has only occurred as the older generation dies off and the younger takes its place.

That's as may be but I find that just as I'm finally starting to learn some stuff that makes it more possible for me to be a better being, understand and want to continue learning about things, and being able to more calmly deal with adversity, and still having plenty of curiosity, the bod is crapping out. Yeah, I'd like to stick around for a while, with the stipulation of reasonably sound mind in a reasonably sound body. Oh, and get off my lawn. [grin]

While I can take your point, I somehow don't see a disaster happening if some of us wanted, decided, and were able to live longer. It would screw up Social Security as it's now run, tho. Besides, given that by mid-century latest half the U.S. workforce will be out of work is a much larger issue.